A novel synthesis of aminofurans using a four-component reaction

Article abstract of DOI:10.1055/s-2007-982540

Protonation of the reactive intermediate produced in the reaction between triphenylphosphine and dialkyl acetylenedicarboxylates by carboxylic acid leads to vinylphosphonium salts, which undergo nucleophilic reaction with carboxylate anion to produce dial

Full text of DOI:10.1055/s-2007-982540

1
610
LETTER
A Novel Synthesis of Aminofurans Using a Four-Component Reaction
N
A
ovel Synthesis of
b
A
minofuran
d
s
U
sing
a
Fo
o
ur-Compone
l
nt Rea
a
ction li Alizadeh,* Sadegh Rostamnia, Nasrin Zoreh, Qasem Oskueyan
Department of Chemistry, Tarbiat Modarres University, P.O. Box 14155-175, Tehran, Iran
Fax +98(21)88006544; E-mail: aalizadeh@modares.ac.ir; E-mail: abdol_alizad@yahoo.com
Received 2 February 2007
dialkyl acetylenedicarboxylate and triphenylphosphine
with suitable OH acids appeared attractive from the view-
point of devising a novel MCR.
Abstract: Protonation of the reactive intermediate produced in the
reaction between triphenylphosphine and dialkyl acetylenedicar-
boxylates by carboxylic acid leads to vinylphosphonium salts,
which undergo nucleophilic reaction with carboxylate anion to
produce dialkyl (E)-2-aroyl-2-butenedioate. This intermediate is
trapped with isocyanide to produce dialkyl 2-(alkylamino)-5-(aryl)-
Although the trapping of the 1:1 intermediate formed be-
tween dialkyl acetylenedicarboxylates and triphenylphos-
phine with OH, NH, and CH acids has been studied in
3
,4-furandicarboxylate.
detail by a number of research groups,1
9–21
trapping of the
Key words: alkyl isocyanide, dialkyl acetylenedicarboxylate, car-
boxylic acid, multicomponent reaction, triphenylphosphine
initially formed 1:1 intermediate with carboxylic acids in
the presence of alkyl isocyanide has not been reported.
We wish to report a simple one-pot four-component reac-
tion between dialkyl acetylenedicarboxylate and triphen-
ylphosphine in the presence of carboxylic acid and alkyl
isocyanide leading to highly functionalized 2-aminofuran
derivatives 4.
Multicomponent reactions (MCRs) have recently
emerged as valuable tools in the preparation of structural-
ly diverse chemical libraries of drug-like heterocyclic
1
compounds. The multicomponent reaction story began as
far back as in 1850 by the publication of the Strecker re- The reaction of triphenylphosphine with dialkyl acetyl-
2
action, arriving nowadays at its apogee. During this one enedicarboxylate 1 in the presence of carboxylic acid 2
and a half century period, some notable achievements in- and alkyl isocyanide 3 preceded spontaneously at room
3
4
clude the discovery of the Biginelli, the Mannich, and temperature in anhydrous CH Cl and finished within a
2
2
5
the Passerini reactions culminating in 1959 when Ugi few hours, to produce dialkyl 2-(alkylamino)-5-(aryl)-
published probably the most versatile MCR based on the 3,4-furandicarboxylate 4 in 69–88% yields (Table 1). The
reactivity of isocyanides. In view of the increasing structures of compounds 4a–g were deduced from their el-
interest in the preparation of large heterocyclic compound emental analysis, IR, and high-field H and C NMR
6
7
1
13
libraries, the development of new and synthetically spectra. The mass spectrum of 4a displayed the molecular
+
valuable multicomponent reactions remains a challenge ion [M ] peak at m/z = 376, which is consistent with the
8
for both academic and industrial research teams.
dimethyl
2-(tert-butylamino)-5-(4-nitrophenyl)-3,4-
furandicarboxylate structure. The IR spectrum of 4a
Substituted furans play an important role in organic chem-
istry, not only as key structural units in many natural
exhibited absorption bands due to the carbonyl group of
–1
–1
9
esters at 1784 and 1669 cm , a NH group at 3445 cm ,
and the absorption bands of the nitro moiety appeared at
products and important pharmaceuticals but also as use-
1
0
ful building blocks in synthetic chemistry. While many
–1
1
591 and 1326 cm .
synthetic routes for furan synthesis exist, convergent
1
annulation strategies without the transition-metal The H NMR spectrum of 4a exhibited four single sharp
1
1,12
catalysis are uncommon.
The unusual reactivity of the lines readily recognized as arising from tert-butyl group
isocyanides functionality offers opportunities for con- (d = 1.52 ppm), methoxy (d = 3.80, 3.95 ppm) and NH
structing substituted heterocyclic compounds and has group (d = 6.7 ppm) protons. The phenyl moiety gave rise
attracted considerable attention in recent years. This reac- to characteristic signals in the aromatic region of the spec-
1
13
tivity involves the a-addition of a nucleophile and an elec- trum. The H decoupled C NMR spectrum of 4a showed
trophile attack on the same carbon atom of the functional 14 distinct resonances in agreement with the dimethyl 2-
1
3–17
group.
Very recently, we reported interesting multi- (tert-butylamino)-5-(4-nitrophenyl)-3,4-furandicarboxy-
component reactions of isocyanides with dimethyl late structure.
acetylenedicarboxylate (DMAD) and aliphatic carboxylic
Although we have not established the mechanism of the
reaction between the triphenylphosphine and the acety-
acids for the synthesis of diaminofuran derivatives.18
In the context of our ongoing studies on heterocyclic con- lenic ester in the presence of carboxylic acid and alkyl
struction mediated by zwitterionic intermediates, the pos- isocyanide in an experimental manner, a possible explana-
sibility of trapping the 1:1 intermediate formed between tion is proposed in Scheme 1. On the basis of the well-
established chemistry of trivalent phosphorus nucleo-
philes,2
2–28
it is reasonable to assume that 4 results from
SYNLETT 2007, No. 10, pp 1610–1612
Advanced online publication: 07.06.2007
DOI: 10.1055/s-2007-982540; Art ID: D03207ST
1
8
.0
6
.2
0
0
7
initial addition of triphenylphosphine to dialkyl acety-
lenedicarboxylate and subsequent protonation of the
©
Georg Thieme Verlag Stuttgart · New York

LETTER
Novel Synthesis of Aminofurans Using a Four-Component Reaction
1611
Table 1 Reaction of Triphenylphosphine and Dialkyl Acetylenedi-
carboxylates 1 in the Presence of Carboxylic Acid 2 and Alkyl Iso-
cyanides 3
In conclusion, the present method carries the advantage
that, not only is the reaction performed under neutral con-
ditions, but also the substances can be mixed without any
activation or modification. The simplicity of the present
procedure makes it an interesting alternative to the com-
plex multistep approaches.
Ph3P
RO2C
CO2R
1
RO2C
CO2R
CH2Cl2
r.t.
R''
COOH
References and Notes
N
H
O
R'
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R'
2
(
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1
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R''
N
C
(
(
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3
(
b) Kappe, O. Acc. Chem. Res. 2000, 33, 879.
4
a
b
c
d
e
f
R
R¢
R¢¢
Yield (%) of 4
(
4) (a) Mannich, C.; Kröschl, W. Arch. Pharm. 1912, 250, 647.
(
(
1
b) Mannich, C. Arch. Pharm. 1917, 255, 261.
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Me
Et
NO2
NO2
H
t-Bu
74
72
69
70
86
84
88
t-Bu
(
(
(
5) (a) Passerini, M. Gazz. Chim. Ital. 1921, 51, 126.
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3
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reactive 1:1 adduct by carboxylic acid, followed by attack
of the carboxylate anion on the positively charged ion 6 to
form dialkyl (E)-2-aroyl-2-butenedioate 7 as intermedi-
ate, which is finally trapped with isocyanide, to give the
corresponding dialkyl 2-(alkylamino)-5-(aryl)-3,4-
1
8
(c) Natural Products Chemistry, Vol. 2; Nakanishi, K.;
Goto, T.; Ito, S.; Natori, S.; Nozoe, S., Eds.; Kodansha:
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furandicarboxylate derivative 4 (see Scheme 1). The
procedure for the preparation of dimethyl 2-(tert-butyl-
amino)-5-(4-nitrophenyl)-3,4-furandicarboxylate (4a) is
2
9
described as an example.
(
1
f) Bock, I.; Bornowski, H.; Ranft, A.; Theis, H. Tetrahedron
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(
10) (a) Lipshutz, B. H. Chem. Rev. 1986, 86, 795. (b) Raczko,
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Ph3P
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Ph3P
1
(11) (a) Cacchi, S. J. Organomet. Chem. 1999, 576, 42. (b)Hou,
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CO2R
5
O
(12) For the synthesis of furans from acyclic precursors, see:
O
O
RO2C
(a) Nair, V.; Vinod, A. U. Chem. Commun. 2000, 1019.
RO2C
H
PPh3
–
Ph3PO
Ar
CO R
3
(
b) Jung, C.-K.; Wang, J. C.; Krische, M. J. J. Am. Chem.
Ar
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CO2R
H
2
6
7
R'
N
R''
C
N
(
e) Ma, S. M.; Zhang, J. L. J. Am. Chem. Soc. 2003, 125,
O
CO2R
H
12386. (f) Yao, T.-L.; Zhang, X. X.; Larock, R. C. J. Am.
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Y.; Reitman, M.; Zhang, Y.; Fathi, R.; Yang, Z. Org. Lett.
O
4
Ar
H
CO2R
Ar
CO2R
CO2R
8
Scheme 1 The proposed mechanism for the reaction of triphenyl-
phosphine and dialkyl acetylenedicarboxylate 1 in the presence of
carboxylic acid 2 and alkyl isocyanide 3.
2002, 4, 2607. (k) Redman, A. M.; Dumas, J.; Scoyy, W. J.
Org. Lett. 2000, 2, 2061. (l) Nakamura, M.; Liang, C.;
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Synlett 2007, No. 10, 1610–1612 © Thieme Stuttgart · New York

1
612
A. Alizadeh et al.
LETTER
(29) To a magnetically stirred solution of 4-nitrobenzoic acid
(
(
(
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D.; Keating, T. A. Acc. Chem. Res. 1996, 29, 123.
(0.17 g, 1 mmol) and dimethyl acetylenedicarboxylate
(0.14 g, 1 mmol) in anhyd CH Cl (5 mL) was added
2
2
dropwise a solution of triphenylphosphine (0.26 g, 1 mmol)
(
(
16) Ugi, I. J. Prakt. Chem. 1997, 339, 499.
17) Dömling, A. Comb. Chem. High Throughput Screening
and tert-butyl isocyanide (0.83 g, 1 mmol) in anhyd CH Cl
2
2
(3 mL) at r.t. over 20 min. The reaction mixture was stirred
for 24 h. The solvent was removed under reduced pressure,
and the residue was separated by silica gel (Merck 230–240
mesh) column chromatography using hexane–EtOAc
mixture as eluent. The product 4a was obtained as orange
crystals; yield: 74% (0.28 g); mp 177–179 °C. IR (KBr):
3445 (NH), 1724 (CO Me), 1669 (CO Me), 1504, 1468
1999, 1, 1.
(
(
18) Alizadeh, A.; Rostamnia, S.; Hu, M. L. Synlett 2006, 1592.
19) Yavari, I.; Alizadeh, A.; Anari-Abbasinejad, M.
Tetrahedron 2003, 59, 6083.
(20) Yavari, I.; Anari-Abbasinejad, M.; Alizadeh, A.; Hossaini,
Z. Tetrahedron 2003, 59, 1289.
2
2
–
1
(21) Alizadeh, A.; Masrouri, H.; Rostamnia, S.; Movahedi, F.
Helv. Chim. Acta 2006, 89, 923.
(Ar), 1591, 1326 (NO ), 1261, 1213, 1184, 1103 (CO) cm .
2
1
H NMR (500.1 MHz, CDCl ): d = 1.52 (s, 9 H, CMe ), 3.79
3
3
(
(
(
22) Zbiral, E. Synthesis 1974, 775.
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(s, 3 H, OMe), 3.96 (s, 3 H, OMe), 6.97 (s, 1 H, NH), 7.61
3
3
(d, J = 8.9 Hz, 2 H, 2 × CH of Ar), 8.22 (d, J = 8.9 Hz,
HH HH
1
3
2 H, 2 × CH of Ar). C NMR: d = 29.81 (CMe ), 51.43
3
1
995, 1895.
25) Johnson, A. W. Ylid Chemistry; Academic Press: New York,
966.
(CMe ), 53.03 (OMe), 53.13 (OMe), 89.65 (C of furan),
3
3
(
117.51 (C of furan), 123.95 (2 × CH of Ar), 124.40 (2 × CH
4
1
of Ar), 134.99 (Cipso), 138.36 (CipsoNO ), 146.00 (C of
2
5
(
(
26) Kolodiazhynyi, O. I. Russ. Chem. Rev. 1997, 66, 225.
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furan), 161.94 (C of furan), 164.58 (CO Me), 165.50
2
2
+
+
(CO Me). MS: m/z (%) = 377 (10) [M + 1], 376 (30) [M ],
2
1
09, 85.
320 (100), 288 (78), 256 (19), 151 (71), 104 (35), 76 (21), 57
(81), 41 (66). Anal. Calcd for C H N O (376.36): C,
(
28) Yavari, I.; Anary-Abbasinejad, M.; Alizadeh, A.
1
8
20
2
7
Tetrahedron Lett. 2002, 43, 4503.
57.44; H, 5.36; N, 7.44. Found: C, 58.00; H, 5.51; N, 7.52.
Synlett 2007, No. 10, 1610–1612 © Thieme Stuttgart · New York

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